The endogenous cholinergic neurotransmitter, acetylcholine, exert its biological effect via two types of cholinergic receptors, the muscarinic Acetyl Choline Receptors (mAChR) and the nicotinic Acetyl Choline Receptors (nAChR).
As it is well established that muscarinic acetylcholine receptors dominate quantitatively over nicotinic acetylcholine receptors in the brain area important to memory and cognition, and much research aimed at the development of agents for the treatment of memory related disorders have focused on the synthesis of muscarinic acetylcholine receptor modulators.
Recently, however, an interest in the development of nAChR modulators has emerged. Several diseases are associated with degeneration of the cholinergic system i.e. senile dementia of the Alzheimer type, vascular dementia and cognitive impairment due to the organic brain damage disease related directly to alcoholism. Indeed several CNS disorders can be attributed to a cholinergic deficiency.
U.S. Pat. No. 3,196,154 (Sterling Drug Inc) describes 3-aryl substituted 3,9-methyl-3,9-diazabicyclo[3.3.1]nonanes, and Fales H M & Barnes R A; J. Am. Chem. Soc. 1954 76 (7) 1947-1948, describe the synthesis of 9-methyl-3,9-diazatricyclo-[3.3.1.23.9]-undecane. However, the 3,9-diaza-bicyclo[3.3.1]nonane derivatives of the present invention are not suggested.